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Molecule in hemoglobin: hidden life as powerful hormone revealed

Released: Wednesday, November 28, 2007

BATON ROUGE – Scientists have made a surprising discovery this week that the iron containing heme molecule, which is a key part of hemoglobin, does a whole lot more than just help deliver oxygen from lungs to the body’s cells. The iron based heme portion of hemoglobin (pronounced HEEM) leads two lives – one in the bloodstream and one within the body’s cells as a powerful hormone that influences weight gain, the sleep cycle, and meal metabolism in ways that could lead to prevention of serious diseases such as obesity, diabetes, depression, sleep disorders and even breast cancer.

Molecular biophysicist Tom Burris, Ph.D., has determined in lab experiments that heme binds with specific receptor proteins in the cytoplasm within cells. Then the heme-protein partnership moves into the nucleus to control specific genes in our DNA, genes that determine how efficiently we use the food we eat, how high our cholesterol levels is, what our sleep cycle is, and even whether we are prone to abnormal weight gain.
“This is a whole new ballgame. Knowing that heme, a very common component within the body, is actually a hormone, allows us to envision a tremendous range of potential medical applications,” said Burris, a researcher at the Pennington Biomedical Research Center. Burris’ work was published this week in Nature Structural and Molecular Biology, an on-line publication of Nature magazine.

According to Burris, hormones and their partner protein receptors are effective tools within the pharmaceutical industry. The hormone estrogen for example, is manufactured and modified to treat breast cancer and osteoporosis, and the hormone cortisol is a common treatment for inflammation.

Heme and its partner protein receptors affect a wide range of bodily functions including whether our bodies use all the food we eat or store it as fat, whether we are prone to weight gain, and even when we sleep and wake. Knowing that heme can control the genes that regulate sleep, metabolism and weight gain could lead to possible hormonal treatments or cures based on modified versions of heme.

“Before we identified them as heme receptors, the proteins we studied were well-known regulators of our internal 24-hour clock, also known as our circadian rhythm. Abnormal circadian rhythms are associated with sleep disorders such as insomnia as well as depression. And people that maintain abnormal 24-hour clocks, such as shift-workers, have a higher incidence of diabetes and obesity. Nurses on shift duty show higher incidence of breast cancer.” Burris said, “If we learn how to control these heme receptors we may be able to provide better therapies for these diseases.”

The newly discovered hormone is likely to be the subject of quick and intense scrutiny and development. Some of Burris’ findings have been duplicated independently in just the last week in work from the University of Pennsylvania.

“The more people looking at the once secret life of heme – as a hormone – the better. Now that we know it, we may have a very powerful tool for future therapies for major metabolic processes, “ Burris said.

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The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the causes of obesity, diabetes, cardiovascular disease, cancer and dementia. Itis a campus of the Louisiana State University System and conducts basic, clinical and population research. The research enterprise at the Center includes approximately 80 faculty and more than 25 post-doctoral fellows who comprise a network of 50 laboratories supported by lab technicians, nurses, dieticians, and support personnel, and 19 highly specialized core service facilities. The Center's more than 500 employees perform research activities in state-of-the-art facilities on the 234-acre campus located in Baton Rouge, Louisiana.